This proposal describes an intensive, five-year training program designed to allow the principal investigator to successfully bridge the gap between clinical and basic science training. The ultimate goal of the performance of this training will be to achieve scientific independence in the fields of normal and malignant hematopoiesis. Dr. Conrad is board certified in pediatrics and is currently a third year pediatric hematology/oncology fellow at the Children's Hospital of Philadelphia. She has been working for the last 18 months in the laboratory of Stephen G. Emerson, M.D., Ph.D. During this time, Dr. Conrad has intensively pursued laboratory investigation and is ready for the next phase of training, progressively independent work. The candidate's research has focused on 1) investigating functional and biological properties of umbilical cord blood (UCB) hematopoietic stem cells (HSCs) and 2) establishing the NOD/SCID assay using cord blood as the source for stem cells. UCB stem cells are not identical to their bone marrow or peripheral blood counterparts, and seem to act as a more primitive population. Immunodeficient mice, including NOD/SCID, have become the preferred in vivo assay for HSCs. Chronic myelogenous leukemia (CML) is believed to be a myeloproliferative disorder of stem-cell origin. Therefore, experiments designed to investigate fundamental questions relating to pathogenesis of CML will be optimized utilizing a system of UCB HSCs and NOD/SCID mice. Dr. Conrad's sponsor, Dr. Emerson, is division chief of the hematology/oncology section at the University of Pennsylvania. He holds a Ph.D. in cell biology and immunology and was scientific director of the alloBMT program at the University of Michigan. He has significantly contributed to and remains committed to Dr. Conrad's growth into a physician scientist.